The overall aim of the Transgenic/Knockout Mouse Core is to provide investigators with access to cutting edge transgenic and knockout mouse technology. Supported exclusively by the USC/Norris Comprehensive Cancer Center for most of the 12 years of its existence, the Core is now a joint resource of the Cancer Center and the Zilkha Neurogenetics Institute. Respectively these institutes provide 60% and 40% of the Core's non-charge back funding, reflecting the current and projected fractional usage. The services offered by the Core are: i) the production of transgenic mice by pronuclear injection; ii) gene targeting in ES cells; iii) injection of targeted ES cells into blastocysts; iv) rederivation of transgenic and knockout lines; and v) cryopreservation of blastocysts to permit "archiving" of mouse strains. During the last grant period, the Core produced mouse models of prostate and ovarian cancer, as well as a transgenic mouse that allows monitoring of endoplasmic reticulum stress in tumors, in vivo. In addition, the Core produced a wide variety of knockout and transgenic mice that have been used to address fundamental questions in cancer biology. The Cancer Center remains strongly supportive both of basic research on the molecular genetic mechanisms underlying cancer and translational research aimed at using discoveries in basic science to improve patient care. Ready access for USC/Norris investigators to transgenic and knockout mouse technology is fundamental to these dual goals.